This invention is related to micro-needles, fabrication of micro-needles, and methods of using the micro-needles for obtaining biological fluid samples and for delivering drugs, agents, formulations or biological molecules across biological tissue barriers.
The detection of analytes in biological fluids is of ever increasing importance. Analyte detection assays find use in a variety of applications, including clinical laboratory testing, home testing, etc., where the results of such testing play a prominent role in the diagnosis and management of a variety of disease conditions. Common analytes of interest include glucose, cholesterol, and the like.
A common technique for collecting a sample of blood for analyte determination is to pierce the skin at least into the subcutaneous layer to access the underlining blood vessels in order to produce localized bleeding on the body surface. The accessed blood is then collected into a small tube for delivery and analyzed by testing equipment, often in the form of a hand-held instrument having a reagent sample onto which the blood sample is placed. The fingertip is the most frequently used site for this method of blood collection due to the large number of small blood vessels located therein. This method has the significant disadvantage of being painful because subcutaneous tissue of the fingertip has a large concentration of nerve endings. This technique of blood sampling also runs the risk of infection and the transmission of disease to the patient, particularly when done on a high-frequency basis. The problems with this technique are exacerbated by the fact that there is a limited amount of skin surface that can be used for the frequent sampling of blood. It is not uncommon for patients who require frequent monitoring of an analyte, to avoid having their blood sampled. With diabetics, for example, the failure to frequently measure their glucose level on a prescribed basis results in a lack of information necessary to properly control the level of glucose. Uncontrolled glucose levels can be very dangerous and even life-threatening.
Similarly, current methods of drug-delivery are invasive and suffer from the same disadvantages as current methods of biological fluid sampling.
To overcome the disadvantages of the above technique and others that are associated with a high degree of pain, certain analyte detection and drug delivery protocols and devices have been developed that use micro-needles, micro-piercing, or micro-cutting elements or analogous structures to penetrate the skin and other tissue barriers. Micro-needles may be combined with analyte measurement systems to provide a minimally invasive fluid retrieval and analyte sensing system. These systems may include one or more micro-needles that penetrate tissue to obtain body fluid samples.
Micro-needles are typically made from stainless steel or other metals. Metal needles are subject to numerous disadvantages. Some of the major disadvantages include the manufacturing complexities of metal needles, such as wire drawing, grinding, deburing and cleaning steps involved in the manufacturing process. Further, impurities in the metals can cause oxidation and deterioration of the needles. As such, the manufacturing process for metal micro-needles may also involve steps where impurities are eliminated from the metals. Another challenge is the difficulty in handling the micro-needles, which are very small and delicate, during each manufacturing step. It may be desirable to provide a certain feature, such as a customized or atypically designed needle tip, that is very difficult if not impossible to do in the conventional fabrication of metal needles. In such a case, the customized feature may require a means for providing or making such a feature which are not completely automated. Customization of metal micro-needles is difficult due to an increase in the number of steps involved in a manufacturing process, the cost of manufacturing and the probability for inconsistent products increase. As such, there is a need in the art for micro-needles that overcome the disadvantages of metal micro-needles.
Despite the work that has already been done in the area of micro-needles and the fabrication thereof, it is desirable to develop a micro-needle that is less expensive and easier to fabricate and customize.
Micro-needles and methods for making and using such micro-needles are provided for the sampling of biological fluid from tissue and/or for the delivery of drugs, etc. to within tissue. The subject micro-needles are useful in the context of analyte concentration measurement and is particularly suited for use in the measurement of glucose concentration in interstitial fluid. The subject micro-needles are also useful for the delivery of drugs for local or systemic therapy or diagnosis. Types of drugs and agents suitable for delivery with the devices of the present invention include, but are not limited to, nucleic acids, proteins, such as growth factors, and other agents such as antibiotics, steroids decongestants anesthetics, etc.
The subject micro-needle has a configuration optimized for minimally invasive sampling of biological fluids and, in particular, interstitial fluid sampling, as well as for the delivery of small doses of drugs or other formulations. A feature of the subject micro-needle is the superior sharpness of its distal tip which may be advantageous in minimizing and eliminating the pain felt by patients, for example, when delivering materials to or withdrawing materials from the skin.
The subject micro-needle is fabricated by means of micro-replication techniques, such as injection molding of a plastic material or the like. The plastic molded injection process allows flexibility in the design of the subject micro-needle and, in particular, allows it to be optimized or customized for a particular intended use.
The micro-needle of the present invention may be used in conjunction with a biological fluid sampling and analyte measuring device or system or with a drug or biological material reservoir or the like. The present invention further includes arrays of the subject micro-needle. Also provided by the present invention are methods of making, methods for using the micro-needle, and kits including one or more of the subject micro-needles or arrays thereof.
These and other features of the invention will become apparent to those persons skilled in the art upon reading the details of the present invention as more fully described below.